The present invention relates to a method for determining a metabolic flux, a program for executing the determination method and a recording medium storing the program.
A metabolic flux analysis, which is also referred to as a flux balance analysis, is a technique for predicting intracellular metabolic flux distributions by construction of a stoichiometric model of intracellular biochemical reactions and linear optimization. This technique has been used in research into the abilities of biochemical reaction systems in microorganisms or for predicting intracellular metabolic flux distributions under different external conditions (Varma, A. and Palsson, B. O. Appl. Environ. Microbiol. 60:3724-3731, 1994; Schilling, C. H. et al., Biotechnol. Prog., 15:288-295, 1999; Schilling, C. H. et al., Biotechnol. Prog., 15:296-303, 1999). It has also been reported that a stoichiometric model was constructed for Escherichia coli (Pramanik, J. and Keasling, J. D., Biotechnol. Bioeng., 56:398-421, 1997; Ibarra, R. U. et al., Nature, 420:186-189, 2002). Also known is an example of using such a stoichiometric model in metabolic engineering for lysine production for Corynebacterium glutamicum, which is used in amino acid production (Vallino, J. J. and Stephanopoulos, G., Biotechnol. Bioeng., 41:633-646, 1993). In addition, a large number of theoretical or experimental methods for metabolic flux analyses and their applications have been reported (Wiechert, W., Journal of Biotechnology, 94:37-63, 2002; Wiechert, W., Metabolic Engineering, 3:195-205, 2001; International Publication No. WO00/46405; International Publication No. WO02/061115; International Publication No. WO02/055995). WO00/46405 discloses a method for predicting a gene required for growth based on a stoichiometric model. WO02/061115 discloses a technique for genetically and evolutionarily changing cells to impart optimal functions to the cells. Further, WO02/055995 discloses a method for applying constraints of qualitative kinetic information, constraints of qualitative metabolic regulation information and constraints based on DNA microarray experimental data under different conditions, to a stoichiometric model. Although all of these are methods for predicting more desirable intracellular metabolic flux distributions, no method has been disclosed for calculating all possible flux distributions satisfying constraints of biological experimental data such as a growth rate and a product production rate.